Selectively fluorinated aromatic compounds are often biologically active and can be used as active components of many drugs and agrochemicals. Nucleophilic substitution of iodide, bromide, and chloride in readily available haloarenes with fluoride can be the easiest, safest, and most efficient way to make fluoroaromatics. Vlasov et al (Russian Chem. Review, 2003 72(8), 681–703) and Adams et al (Chem. Soc. Rev., 1999, 28, 225–231) reviewed fluorination methods by halogen and nitro exchange, but in all cases the aromatic compound was activated toward the displacement with fluoride by other moieties on the ring.
Existing methods to fluorinate nonactivated aromatic rings are expensive, impractical and yield low amounts of the desired compounds. The best-known method for fluorination of nonactivated aromatic rings is the Balz-Schiemann reaction, which uses expensive, toxic and potentially explosive diazonium salts at elevated temperatures. Other methods use the even more toxic thallium, mercury, and lead compounds, or costly iodonium salts (Grushin, V., Chem. Eur. J., 2002, 8, No. 5). In U.S. Pat. No. 6,166,273 benzene was fluorinated by the non-catalytic reaction with CuF2 to producing Cu metal, but this reaction was run only in the gas phase.
What is needed, then, is a better and safer catalytic method for the introduction of fluorine into the aromatic ring, especially of nonactivated aromatic compounds. The applicant has discovered a new method for the preparation of fluoroarenes via the use of copper (II) fluoride in the presence of some bidentate tertiary amine ligands.